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SNP imputation in association studies

Nature Biotechnology volume 27, pages 349–351 (2009)Cite this article

Only a subset of single-nucleotide polymorphisms (SNPs) can be genotyped in genome-wide association studies. Imputation methods can infer the alleles of 'hidden' variants and use those inferences to test the hidden variants for association.

The large amount of data generated in whole-genome association studies, involving hundreds of thousands of SNPs genotyped in thousands of individuals, complicates the statistical and computational analysis of that data. The correlation between SNPs (linkage disequilibrium) enables much of the variation to be captured despite the inability to genotype all SNPs, and our previous primer1 described how tagSNPs and haplotypes have been used as proxies for neighboring associations. However, especially with the advent of high-throughput genotyping technologies, the key challenge has started to shift from identifying tagSNPs that best capture genetic variation in the population to the ability to interrogate SNPs not covered by these technologies. Moreover, how does one consolidate distinct data sets when subsets of the same population are genotyped with slightly different technologies that have different capacities?

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Figure 1: Models used in imputation methods.

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Acknowledgements

E.H. is a faculty fellow of the Edmond J. Safra Bioinformatics program at Tel Aviv University. E.H. was supported by National Science Foundation grant IIS-071325412 and by the Israel Science Foundation grant no. 04514831.

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Authors and Affiliations

  1. and the Blavatnik School of Computer Science and the Department of Biotechnology, Eran Halperin is at the International Computer Science Institute, Berkeley, California, USA, Tel Aviv University, Tel Aviv, Israel.,

    Eran Halperin

  2. Dietrich A. Stephan is in the Division of Genomics Research, Navigenics, Foster City, California, USA.,

    Dietrich A Stephan

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  1. Eran Halperin
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  2. Dietrich A Stephan
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Correspondence to Dietrich A Stephan.

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Halperin, E., Stephan, D. SNP imputation in association studies. Nat Biotechnol 27, 349–351 (2009). https://doi.org/10.1038/nbt0409-349

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